Affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing Advanced Institute for Life Sciences (NAILS), Nanjing University School of Life Sciences, Nanjing, 210093, China.

ABSTRACTMicroRNAs (miRNAs) are a class of noncoding RNAs that regulates target gene expression at posttranscriptional level, leading to further biological functions. We have demonstrated that microvesicles (MVs) can deliver miRNAs into target cells as a novel way of intercellular communication. It is reported that in central nervous system, glial cells release MVs, which modulate neuronal function in normal condition. To elucidate the potential role of glial MVs in disease, we evaluated the effects of secreted astrocytic MVs on stress condition. Our results demonstrated that after Lipopolysaccharide (LPS) stimulation, astrocytes released shedding vesicles (SVs) that enhanced vulnerability of dopaminergic neurons to neurotoxin. Further investigation showed that increased astrocytic miR-34a in SVs was involved in this progress via targeting anti-apoptotic protein Bcl-2 in dopaminergic neurons. We also found that inhibition of astrocytic miR-34a after LPS stimulation can postpone dopaminergic neuron loss under neurotoxin stress. These data revealed a novel mechanism underlying astrocyte-neuron interaction in disease.

Mentions:
Next, we investigated the impact of astrocyte-derived microvesicles under stress conditions on cell survival. We found that neither SVs nor exosomes derived from the LPS-stimulated U87-MG astroglial cell line had any effects on SH-SY5Y cell viability under normal conditions (Fig. S1). However, further investigation showed that pretreatment of SVs derived from LPS-stimulated U87-MG cells increased the vulnerability of the SH-SY5Y cells to threshold concentrations of neurotoxins, such as 0.2 mmol/L MPP+ or 10 μmol/L 6-OHDA (Figs. 2A, 2B and S1).Figure 2

Mentions:
Next, we investigated the impact of astrocyte-derived microvesicles under stress conditions on cell survival. We found that neither SVs nor exosomes derived from the LPS-stimulated U87-MG astroglial cell line had any effects on SH-SY5Y cell viability under normal conditions (Fig. S1). However, further investigation showed that pretreatment of SVs derived from LPS-stimulated U87-MG cells increased the vulnerability of the SH-SY5Y cells to threshold concentrations of neurotoxins, such as 0.2 mmol/L MPP+ or 10 μmol/L 6-OHDA (Figs. 2A, 2B and S1).Figure 2

Affiliation:
State Key Laboratory of Pharmaceutical Biotechnology, Nanjing Advanced Institute for Life Sciences (NAILS), Nanjing University School of Life Sciences, Nanjing, 210093, China.

ABSTRACTMicroRNAs (miRNAs) are a class of noncoding RNAs that regulates target gene expression at posttranscriptional level, leading to further biological functions. We have demonstrated that microvesicles (MVs) can deliver miRNAs into target cells as a novel way of intercellular communication. It is reported that in central nervous system, glial cells release MVs, which modulate neuronal function in normal condition. To elucidate the potential role of glial MVs in disease, we evaluated the effects of secreted astrocytic MVs on stress condition. Our results demonstrated that after Lipopolysaccharide (LPS) stimulation, astrocytes released shedding vesicles (SVs) that enhanced vulnerability of dopaminergic neurons to neurotoxin. Further investigation showed that increased astrocytic miR-34a in SVs was involved in this progress via targeting anti-apoptotic protein Bcl-2 in dopaminergic neurons. We also found that inhibition of astrocytic miR-34a after LPS stimulation can postpone dopaminergic neuron loss under neurotoxin stress. These data revealed a novel mechanism underlying astrocyte-neuron interaction in disease.